The Human Placenta in Gestational Diabetes Mellitus

The placenta is a complex fetal organ that fulfills pleiotropic roles during fetal growth. It separates the maternal and fetal circulation, with which it is in contact through different surfaces, i.e., the syncytiotrophoblast exposes the placenta to the maternal circulation and the endothelium is in contact with fetal blood. Because of this unique position, the placenta is exposed to the regulatory influence of hormones, cytokines, growth factors, and substrates present in both circulations and, hence, may be affected by changes in any of these. In turn, it can produce molecules that will affect mother and fetus independently. The human placenta expresses virtually all known cytokines including tumor necrosis factor (TNF)-α, resistin, and leptin, which are also produced by the adipose cells. The discovery that some of these adipokines are key players in the regulation of insulin action suggests possible novel interactions between the placenta and adipose tissue in understanding pregnancy-induced insulin resistance. The interplay between the two systems becomes more evident in gestational diabetes mellitus (GDM). In diabetes, the placenta undergoes a variety of structural and functional changes (rev. in 1–3). Their nature and extent depend on a range of variables including the quality of glycemic control achieved during the critical periods in placental development, the modality of treatment, and the time period of severe departures from excellent metabolic control of a nondiabetic environment. Placental development is characterized by three distinct periods. At the beginning of gestation, a series of critical proliferation and differentiation processes predominantly of the trophoblast eventually lead to the formation of villous and extravillous structures. The latter anchor the placenta in the uterus and remodel the uterine spiral arteries into low resistance vessels. Then the newly formed villi differentiate through various steps of maturation. The end of gestation is associated with placental mass expansion, …